Common and idiosyncratic patterns of cytokine gene expression by Epstein-Barr virus transformed human B cell lines.
Epstein-Barr virus (EBV) transformed human B cells proliferate indefinitely in vitro, and it has been proposed that cytokine-mediated autocrine loops contribute to the maintenance of the lymphoblastoid phenotype. We used a novel multiprobe RNase protection assay to quantify cytokine mRNA species expressed by EBV-transformed lymphoblastoid cell lines (LCL), derived either by the transformation of B cells with B95-8 or wild-type EBV or by the in vitro outgrowth of EBV-associated B cell lymphomas to identify cytokines that are commonly expressed in all LCL and thus more likely to be essential for immortalization of B cells. All 16 LCL expressed high levels of tumor necrosis factor (TNF)alpha, TNFbeta, and transforming growth factor (TGF)beta1 mRNA, while interleukin (IL)-10 transcripts were detected in most LCL but at a lower level. Expression of IL-1alpha, IL-1beta, IL-6, IL-12p35, IL-12p40, IL-13 and IFNgamma mRNA was variable among the LCL tested. Granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, IL-4, and IL-5 mRNA were undetectable in all LCL. Furthermore, we found that IL-10, TNFalpha, and TNFbeta mRNA were induced in EBV-negative B cell lines after infection with EBV. These data define common versus idiosyncratic patterns of cytokine expression by LCL and, in the former case, such cytokines as TNFalpha, TNFbeta, and IL-10 emerge as strong candidates that are essential for the autocrine regulation of EBV-immortalized B cells.
Rochford
R
R
Department of Immunology, The Scripps Research Institute, La Jolla, California, USA.
Cannon
M J
MJ
Sabbe
R E
RE
Adusumilli
K
K
Picchio
G
G
Glynn
J M
JM
Noonan
D J
DJ
Mosier
D E
DE
Hobbs
M V
MV
D000818:Animals; D002461:Cell Line, Transformed / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D012260:Ribonucleases / Q000737:chemistry; D013698:Templates, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012260:Ribonucleases